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CYP3A5 genotype impacts maraviroc pharmacokinetics in healthy volunteers (1141.15)
Author(s) -
Lu Yanhui,
Hendrix Craig,
Bumpus Namandjé
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.1141.15
Subject(s) - cmax , pharmacokinetics , maraviroc , cyp3a5 , pharmacology , genotype , allele , medicine , chemistry , biology , immunology , genetics , human immunodeficiency virus (hiv) , gene
We have demonstrated in vitro that the polymorphic enzyme cytochrome P450 3A5 (CYP3A5) plays a major role in the oxidative metabolism of the anti‐HIV drug maraviroc. The present study evaluated the impact of CYP3A5 genotype on the pharmacokinetics of maraviroc. Of the sixteen subjects enrolled, 8 subjects carried the CYP3A5*1 allele (3 CYP3A5*1 homozygous and 5 heterozygous) and 8 subjects did not carry the CYP3A5*1 allele. Subjects received an oral dose of 300 mg maraviroc and blood was sampled over a period of 32 hr. Plasma maraviroc concentrations were determined using liquid chromatography‐mass spectrometry and pharmacokinetic parameters including area under the plasma concentration‐time curve (AUCinf), peak concentration (Cmax), and clearance were calculated. The pharmacokinetic parameters did not differ between the group carrying the CYP3A5*1 allele versus those not carrying a CYP3A5*1 allele. However, the CYP3A5*1 homozygous group exhibited 55% and 52% lower AUCinf, 97% and 84% higher apparent clearance, and 65% and 59% lower Cmax, respectively, as compared to the subjects that were heterozygous for CYP3A5*1 and those not carrying the CYP3A5*1 allele. In conclusion, Cmax and AUCinf were decreased while clearance was increased in subjects carrying two CYP3A5*1 alleles. The results indicate maraviroc has the potential to be used as a CYP3A5 clinical phenotyping probe. Grant Funding Source : Supported by The Johns Hopkins ICTR ATIP Grant